Stroke is a leading cause of morbidity and mortality in the United States and throughout the world. The purpose of the proposed research project is to characterize in vivo brain parenchymal changes in a rat model of focal stroke with reperfusion using magnetic resonance (MR) techniques. Functional assessment of the ischemic region will be carried out using a novel technique for noninvasive quantitative MR imaging of tissue perfusion, which will be used to acquire time-resolved perfusion images following acute focal stroke and subsequent reperfusion. Further characterization will be carried out using various other types of MR imaging methods which yield complementary types of tissue contrast, and comparison will be made using histopathologic analysis in the chronic stage as a "gold standard' of brain infarction and recovery. These techniques will be used to determine the MR correlates of the "ischemic penumbra", namely the regions of potentially reversible ischemia injury. Once the MR correlates are determined, the effects of various therapies aimed at reducing tissue damage in brain ischemia can be readily tested using this model. Because MR techniques are noninvasive, this approach is immediately applicable to the investigation and therapy of acute stroke in humans. For example, the accurate determination of potentially salvageable brain tissue in a patient with acute stroke would improve the risk-benefit ratio for thrombolytic therapy or other therapies which carry significant risks. To this end, technical development of the MR perfusion technique for use in humans will take place simultaneously with the rat studies.